Perspectives on spreading depression

Reentrant spiral waves of spreading depression cause macular degeneration in hypoglycemic chicken retina

“…SD velocity was uniform throughout the central and peripheral retinal regions, and did not differ in either the nasotemporal or dorsoventral axes. This spread velocity falls into the range of propagation velocities observed for SDs in other regions, species, and preparations (1.7-9.7 mm/min) (6)(7)(8)(9). In the wake of a wave of SD, the retinal tissue remained refractory to further waves for a period of 120 ± 4 s (n = 15 measurements; n = 5 retinas; Fig.…”

“…The field potentials were largest in the inner plexiform layer (Fig. 2) (8) and inverted close to the outer plexiform layer. Under normal oxygen and glucose conditions, SD waves could be elicited every 15 min over 4 h without either tissue damage or a change in the field potential (Figs.…”

“…SD results in transient elevations of the extracellular K + concentration of 30-80 mM in the intact nervous tissue ascribable to depolarization-induced K + and Na + activation and excitatory transmitter release (8), although the failure of TTX to block SD indicates that Na + channel activation in not essential. We found that relatively small increases in extracellular K + -altered from 4 to 6 to 8 mM-are sufficient to increase the "excitability" of the central retina for generation of SD waves with respect to both shortening of the refractory period and an increase in the number of spontaneous radial SDs/h (Fig.…”

“…SD is a slow diffusion-mediated self-sustained wave of generalized depolarization of gray matter or retina that does not respect synaptic connectivity (7) and severely disrupts neuronal function. SD results in a temporary collapse of transmembrane ionic gradients and membrane potential (8,9), and is characterized by a negative field potential 10-20 mV in amplitude and 1-2 min in duration, propagating at a velocity of a few millimeters per minute (6)(7)(8)(9)(10). The advancing wave front is accompanied by a burst of action potentials and K + efflux into the interstitial space, followed by electrical silence, which is associated with the negative field potential (11,12).…”

“…Hypoglycemia, a condition that facilitates the initiation of cerebral SD in rats (17), appears to lead to retinal cell death and gradual loss of visual acuity in aging mice (15). Here we used the ex vivo chicken retina, an established system in which waves of SD can be visualized as areas of increased light scattering (8). We found that in hypoglycemic retina, a small number of spontaneous or evoked episodes of SD cause irreversible punctate lesions in the macula.…”